Permethrin

P03A - Ectoparasiticides ATC P03AC04 Small molecule approved 1986 Topical Natural product Withdrawn

JFDA label: Prescab 5% Cream

Mechanism of Action

Blocker of Voltage-sensitive sodium channel — Voltage-sensitive sodium channel blocker

Target	Action	Gene / class
Voltage-sensitive sodium channel efficacy	BLOCKER	vssc

Indications

Approved

Head lice (lotion/cream rinse)
Scabies (cream)

Off-label

Pubic lice (Pediculosis pubis)
Scabies, crusted (Norwegian scabies)

Contraindications

Source: Lexicomp

Hypersensitivity to any pyrethroid or pyrethrin, or to any component of the formulation. OTC labeling (cream rinse/lotion): When used for self-medication, do not use on infants Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (4)

Common Local discomfort (scalp) · localized burning · localized numbness · tingling of skin

Skin and subcutaneous tissue disorders (4)

Common erythema · Pruritus · skin rash (scalp) · stinging of the skin

General disorders and administration site conditions (1)

Common Localized edema

Dosing

Source: Lexicomp

Head lice: Topical: Cream rinse/lotion 1%: Prior to application, wash hair with conditioner-free shampoo; rinse with water and towel dry. Apply a sufficient amount of lotion or cream rinse to saturate the hair and scalp (especially behind the ears and nape of neck). Leave on hair for 10 minutes (but no longer), then rinse off with warm water; remove remaining nits with nit comb. A single application is generally sufficient; however, may repeat 7 days after first treatment if lice or nits are still present. Pubic lice (off-label use): Topical: Cream rinse 1%: Apply to affected areas and wash off after 10 minutes (CDC [Workowski 2015]). Scabies: Topical: Cream 5%: Thoroughly massage cream (30 g for average adult) from head to soles of feet; leave on for 8 to 14 hours before removing (shower or bath); for infants and the elderly, also apply on the hairline, neck, scalp, temple, and forehead; may repeat if living mites are observed 14 days after first treatment; one application is generally curative. Scabies, crusted (Norwegian scabies) (off-label use): Topical: Cream 5%: Apply to entire body; leave on for 8 to 14 hours before washing off with water. Repeat this regimen daily for 7 days, and then twice weekly until symptoms have resolved. Ivermectin should be given concomitantly on days 1, 2, 8, 9, and 15 (and potentially on days 22 and 29 for severe cases) (CDC [Workowski 2015]).

(For additional information see "Permethrin: Pediatric drug information") Head lice: Topical: Cream rinse/lotion 1%: Infants ≥2 months, Children, and Adolescents: Refer to adult dosing. Scabies: Topical: Cream 5%: Infants ≥2 month, Children, and Adolescents: Refer to adult dosing.

When treating scabies in elderly patients, also apply on the hairline, neck, scalp, temple, and forehead. Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling. Since topical permethrin is metabolized in the liver and excreted in the urine as inactive metabolites, there does not appear to be an increased risk of toxic reactions in patients with impaired renal function.

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Skin irritation

Treatment may temporarily exacerbate the symptoms of itching, redness, and swelling. Discontinue use if hypersensitivity occurs. Other warnings/precautions:

Appropriate use

For external use only. Avoid contact with eyes.

Ragweed allergy (cream rinse/lotion)

May cause difficulty in breathing or an asthmatic attack.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events have not been observed in oral animal reproduction studies. The amount of permethrin available systemically following topical application is ≤2%. The CDC considers the use of permethrin or pyrethrins with piperonyl butoxide the drugs of choice for the treatment of pubic lice during pregnancy; permethrin is the preferred treatment of scabies during pregnancy (CDC [Workowski 2015]).

Lactation

It is not known if permethrin is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother. Lactating women may be treated with permethrin (CDC [Workowski 2015]).

Chemistry & Properties

Formula	C21H20Cl2O3
Molecular weight	391.29 g/mol
IUPAC name	(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate
CAS	52645-53-1
PubChem CID	40326
InChIKey	`RLLPVAHGXHCWKJ-UHFFFAOYSA-N`
logP	6.11 (XLogP 6.5)
Polar surface area	35.53 Å²
H-bond acceptors / donors	3 / 0
Drug-likeness (QED)	0.56
Lipinski violations	1

SMILES

CC1(C)C(C=C(Cl)Cl)C1C(=O)OCc1cccc(Oc2ccccc2)c1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Inhibitor	—
CYP2B6	Inhibitor	—
CYP2B6	Substrate	—
CYP2C19	Inhibitor	—
CYP2C19	Substrate	—
CYP2C8	Inhibitor	—
CYP2C9	Inhibitor	—
CYP2C9	Substrate	—
CYP2D6	Inhibitor	—
CYP3A4	Inhibitor	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Prescab Cream	Cream 2 %	60 g tube	Arab Center for Pharmaceuticals & Chemicals	2.390
Prescab	Cream 50 mg/g	60 g tube	Arab Center for Pharmaceuticals & Chemicals	3.290